Natural history and development of a novel composite endpoint in patients with alcohol-associated Hepatitis: Data from a prospective multicenter study.

Dasarathy S, Tu W, Welch N, Gawrieh S, Yu Y, Tang Q, Kettler C, Sanyal AJ, Szabo G, Shah VH, Bataller R, Nagy LE, McClain C, Chalasani N, Kerr T, Mitchell M, Investigators for A. Natural history and development of a novel composite endpoint in patients with alcohol-associated Hepatitis: Data from a prospective multicenter study.. Hepatology (Baltimore, Md.). 2025; PMID: 40924794

Abstract

BACKGROUND: The clinical course and outcomes of alcohol-associated hepatitis (AH) remain poorly understood. Major adverse liver outcomes (MALO) do not capture the added risk of return to drinking (RTD). We examined the natural history of AH and developed a composite endpoint using a contemporary observational cohort of AH.

METHODS: A cohort of 1127 participants: 712 AH patients, 256 heavy drinking (HD) controls without clinically evident liver disease, and 159 healthy controls, were prospectively followed for 6-months at eight United States centers as part of the Alcoholic Hepatitis Network (AlcHepNet) consortium. Outcomes included mortality and a composite endpoint (AlcHepNet composite index) that included death, liver transplantation, hepatic decompensation (new onset/worsening ascites, hepatic encephalopathy, variceal bleeding), liver-related hospital admission, MELD increase ≥5, and return to drinking (RTD).

RESULTS: Of 712 AH patients (age 45±10.7 y; 59.1% male), 558 (79.0%) had severe and 148 (21.0%) had moderate AH, 232 (32.5%) died, and 86 (12.1%) underwent liver transplantation. Mortality rates in moderate AH and severe AH were 0.7% versus 17.2% (30 d), 3.4% versus 26.5% (90 d), and 8.8% versus 30.5% (180 d), respectively (all p<0.001). Composite liver/alcohol use events were noted in 459 (64.5%) AH patients. Higher MELD score, lower mean arterial pressure, and baseline leukocytosis were associated with higher 90-day mortality in AH (all p<0.05). College education and higher alkaline phosphatase were associated with lower mortality. HD controls had low mortality (n=3; 1.2%).

DISCUSSION: This large observational study showed a high incidence of composite liver and alcohol-use events within six months, reiterating the need for early interventions.

Last updated on 09/10/2025
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